Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
Andre C. Kalil,Thomas F. Patterson,Aneesh K. Mehta,Kay M. Tomashek,Cameron R. Wolfe,Varduhi Ghazaryan,Vincent C. Marconi,Guillermo M. Ruiz-Palacios,Lanny Hsieh,Susan Kline,Victor F. Tapson,Nicole M. Iovine,Mamta K. Jain,Daniel A. Sweeney,Hana M. El Sahly,Angela Branche,Justino Regalado Pineda,David C. Lye,Uriel Sandkovsky,Anne F Luetkemeyer,Stuart H. Cohen,Robert W. Finberg,Patrick E. H. Jackson,Babafemi Taiwo,Catharine I. Paules,Henry Arguinchona,Nathaniel B. Erdmann,Neera Ahuja,Maria G. Frank,Myoung Don Oh,Eu-Suk Kim,Seow Y Tan,Richard A. Mularski,Henrik Nielsen,Philip O Ponce,Barbara S. Taylor,LuAnn Larson,Nadine Rouphael,Youssef Saklawi,Valeria D Cantos,Emily R Ko,John J. Engemann,Alpesh Amin,Miki Watanabe,Joanne Billings,Marie-Carmelle Elie,Richard T. Davey,Timothy Burgess,Jennifer Ferreira,Michelle Green,Mat Makowski,Anabela Cardoso,Stephanie de Bono,Tyler Bonnett,Michael A. Proschan,Gregory A. Deye,Walla Dempsey,Seema U Nayak,Lori E. Dodd,John H. Beigel +59 more
TLDR
Baricitinib plus remdesivir was superior to remdes Vivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation.Abstract:
Background Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. Results A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). Conclusions Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).read more
Citations
More filters
Journal ArticleDOI
A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19
Yeon Sook Kim,Seng-Ho Jeon,Jung-Hwa Kim,Jong-Hoon Koh,Seung Won Ra,Ji Won Kim,Yeonjae Kim,Choon Kwan Kim,Yun Chul Shin,Beodeul Kang,Seung-Ji Kang,Chul-Hee Park,Bo Yeon Lee,Ji-Yeon Lee,Chung Hoon Lee,Jae-Phil Choi,Jin Yong Kim,Shinae Yu,Kyong Ran Peck,Sung-Han Kim,Jung Yeon Heo,Hyun Kim,Hyun Jin Park,Jong Hyung Choi,Jumi Han,Joohyun Kim,Hyoung-Jun Kim,Se-Hee Han,A-Ran Yoon,Mihee Park,Sujung Park,Yu Kyung Kim,Mi-Kyung Jung,Myoung Don Oh +33 more
TL;DR: In this article , a randomized, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients was conducted, where patients were randomized to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days.
Journal ArticleDOI
Organotypic human ex vivo models for coronavirus disease 2019 research and drug development.
TL;DR: A mini-review summarizes recent work to study SARS-CoV-2 infection in human 3D tissue models with an emphasis on the pharmacological tools that have been developed to understand and prevent viral entry and replication as discussed by the authors.
Journal ArticleDOI
COVID-19 and cardiovascular disease: manifestations, pathophysiology, vaccination, and long-term implication
TL;DR: Cardiovascular involvement in the COVID-19 pandemic is reviewed with respect to clinical features, pathogenesis, long-term effects, and the adverse effects of treatments and vaccines based on the latest evidence.
Journal ArticleDOI
Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.
Wesley H. Self,Matthew S. Shotwell,Kevin W Gibbs,Marjolein de Wit,D. Clark Files,Michelle Harkins,Kristin M. Hudock,Lisa H. Merck,Ari Moskowitz,Krystle Apodaca,Aaron N. Barksdale,Basmah Safdar,Ali Javaheri,Jeffrey M. Sturek,Harry M Schrager,Nicole M. Iovine,Ivor S. Douglas,Joseph E. Levitt,Laurence W. Busse,Adit A. Ginde,Sam Brown,David N. Hager,Katherine L. Boyle,Abhijit Duggal,Akram Khan,Michael J. Lanspa,Peter Chen,Michael A. Puskarich,Derek J Vonderhaar,Lokesh Venkateshaiah,Nina T. Gentile,Yves Rosenberg,James Troendle,Amanda J. Bistran-Hall,Josh DeClercq,Robert R. Lavieri,Meghan Morrison Joly,Jill M. Pulley,Todd W. Rice,Jonathan S. Schildcrout,Matthew W. Semler,Lei Wang,Gordon R. Bernard,Sean Collins +43 more
TL;DR: In this paper , the authors evaluated the efficacy and safety of RAS modulation using two investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angio-ensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angioensin (1 − 7) and mitigate the action (2 − 5) and may be an important contributor to COVID-19 pathophysiology.
Journal ArticleDOI
Evaluation of the Treatment Efficacy and Safety of Remdesivir for COVID-19: a Meta-analysis.
Jun Tao,Rebecca Aristotelidis,Alexandra Zanowick-Marr,Laura C Chambers,James B. McDonald,Eleftherios Mylonakis,Philip A. Chan +6 more
TL;DR: In this article, the authors conducted a meta-analysis to systematically identify and synthesize existing findings from six electronic databases and unpublished studies and found that patients on remdesivir were 17% (RR 0.83, 95% CI: 0.65, 1.06) less likely to die than those within the control group.
References
More filters
Journal ArticleDOI
COVID-19: consider cytokine storm syndromes and immunosuppression
Puja Mehta,Daniel F. McAuley,Michael Brown,Emilie Sanchez,Rachel Tattersall,Rachel Tattersall,Jessica J Manson +6 more
TL;DR: Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.
Journal ArticleDOI
Remdesivir for the Treatment of Covid-19 - Final Report.
John H. Beigel,Kay M. Tomashek,Lori E. Dodd,Aneesh K. Mehta,Barry S. Zingman,Andre C. Kalil,Elizabeth L. Hohmann,Helen Y. Chu,Annie Luetkemeyer,Susan Kline,Diego Lopez de Castilla,Robert W. Finberg,Kerry Dierberg,Victor F. Tapson,Lanny Hsieh,Thomas F. Patterson,Roger Paredes,Daniel A. Sweeney,William R. Short,Giota Touloumi,David Chien Lye,Norio Ohmagari,Myoung-don Oh,Guillermo M. Ruiz-Palacios,Thomas Benfield,Gerd Fätkenheuer,Mark G. Kortepeter,Robert L. Atmar,C. Buddy Creech,JD Lundgren,Abdel G. Babiker,Sarah Pett,James D. Neaton,Timothy Burgess,Tyler Bonnett,Michelle Green,Mat Makowski,Anu Osinusi,Seema U Nayak,H. Clifford Lane +39 more
TL;DR: The data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.
Journal ArticleDOI
Dexamethasone in Hospitalized Patients with Covid-19
Peter Horby,Wei Shen Lim,Jonathan Emberson,M Mafham,Jennifer L Bell,Louise Linsell,Natalie Staplin,Christopher E. Brightling,Andrew Ustianowski,E Elmahi,B Prudon,Christopher A Green,Timothy Felton,David Chadwick,K Rege,C Fegan,Lucy C Chappell,Saul N. Faust,Thomas Jaki,Katie Jeffery,Alan A Montgomery,Kathryn M Rowan,Edmund Juszczak,J K Baillie,Richard Haynes,Martin J Landray +25 more
TL;DR: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
Journal ArticleDOI
Baricitinib as potential treatment for 2019-nCoV acute respiratory disease.
Peter D. Richardson,Ivan Griffin,Catherine Tucker,Daniel J. Smith,Olly Oechsle,Anne Phelan,Michael J. Rawling,Edward Savory,Justin Stebbing +8 more
TL;DR: It is suggested that baricitinib could be trialled, using an appropriate patient population with 2019-nCoV acute respiratory disease, to reduce both the viral entry and the inflammation in patients, using endpoints such as the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia.
Journal ArticleDOI
COVID-19: combining antiviral and anti-inflammatory treatments
Justin Stebbing,Anne Phelan,Ivan Griffin,Catherine Tucker,Olly Oechsle,Daniel J. Smith,Peter D. Richardson +6 more
TL;DR: Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury, and convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.
Related Papers (5)
Dexamethasone in Hospitalized Patients with Covid-19
Peter Horby,Wei Shen Lim,Jonathan Emberson,M Mafham,Jennifer L Bell,Louise Linsell,Natalie Staplin,Christopher E. Brightling,Andrew Ustianowski,E Elmahi,B Prudon,Christopher A Green,Timothy Felton,David Chadwick,K Rege,C Fegan,Lucy C Chappell,Saul N. Faust,Thomas Jaki,Katie Jeffery,Alan A Montgomery,Kathryn M Rowan,Edmund Juszczak,J K Baillie,Richard Haynes,Martin J Landray +25 more
Remdesivir for the Treatment of Covid-19 - Final Report.
John H. Beigel,Kay M. Tomashek,Lori E. Dodd,Aneesh K. Mehta,Barry S. Zingman,Andre C. Kalil,Elizabeth L. Hohmann,Helen Y. Chu,Annie Luetkemeyer,Susan Kline,Diego Lopez de Castilla,Robert W. Finberg,Kerry Dierberg,Victor F. Tapson,Lanny Hsieh,Thomas F. Patterson,Roger Paredes,Daniel A. Sweeney,William R. Short,Giota Touloumi,David Chien Lye,Norio Ohmagari,Myoung-don Oh,Guillermo M. Ruiz-Palacios,Thomas Benfield,Gerd Fätkenheuer,Mark G. Kortepeter,Robert L. Atmar,C. Buddy Creech,JD Lundgren,Abdel G. Babiker,Sarah Pett,James D. Neaton,Timothy Burgess,Tyler Bonnett,Michelle Green,Mat Makowski,Anu Osinusi,Seema U Nayak,H. Clifford Lane +39 more
Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.
Hongchao Pan,Richard Peto,Ana-Maria Henao-Restrepo,Marie-Pierre Preziosi,Vasee Sathiyamoorthy,Quarraisha Abdool Karim,Marissa M. Alejandria,César Hernández García,Marie-Paule Kieny,Reza Malekzadeh,Srinivas Murthy,K. Srinath Reddy,Mirta Roses Periago,Pierre Abi Hanna,Florence Ader,Abdullah M. Al-Bader,Almonther Alhasawi,Emma Allum,Athari Alotaibi,Carlos A Alvarez-Moreno,Sheila Appadoo,Abdullah Asiri,Pål Aukrust,Andreas Barratt-Due,Samir Bellani,Mattia Branca,Heike B. C. Cappel-Porter,Nery Cerrato,Ting S. Chow,Najada Como,Joseph A. Eustace,Patricia J. Garcia,Sheela Godbole,Eduardo Gotuzzo,Laimonas Griskevicius,Rasha Hamra,Mariam Hassan,Mohamed Hassany,David Hutton,Irmansyah Irmansyah,Ligita Jancoriene,Jana Kirwan,Suresh Kumar,Peter Lennon,Gustavo Lopardo,Patrick Lydon,Nicola Magrini,Teresa Maguire,Suzana Manevska,Oriol Manuel,Sibylle McGinty,Marco T. Medina,María L. Mesa Rubio,Maria C. Miranda-Montoya,Jeremy Nel,Estevão Portela Nunes,Markus Perola,Antonio Portolés,Menaldi R. Rasmin,Aun Raza,Helen Rees,Paula P. S. Reges,Chris A Rogers,Kolawole Salami,Marina I. Salvadori,Narvina Sinani,Jonathan A C Sterne,Milena Stevanovikj,Evelina Tacconelli,Kari A.O. Tikkinen,Sven Trelle,Hala Zaid,John-Arne Røttingen,Soumya Swaminathan +73 more
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more